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Acta Pharmacologica Sinica May 2022Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are...
Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary function test, as well as markers for inflammation and fibrosis. Moreover, using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice, our results provide a novel description of the target pathways for tetrandrine. Specifically, we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages. Taken together, our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets. Our results also facilitated the wider adoption and development of tetrandirne, potentially accelerating a globally accepted therapeutic strategy for silicosis.
Topics: Animals; Benzylisoquinolines; Fibrosis; Inflammasomes; Inflammation; Lung; Macrophages; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Silicosis
PubMed: 34417574
DOI: 10.1038/s41401-021-00693-6 -
Theranostics 2021: Silicosis is a severe occupational lung disease. Current treatments for silicosis have highly limited availability ( lung transplantation) or, do not effectively...
: Silicosis is a severe occupational lung disease. Current treatments for silicosis have highly limited availability ( lung transplantation) or, do not effectively prolong patient survival time ( lung lavage). There is thus an urgent clinical need for effective drugs to retard the progression of silicosis. : To systematically characterize the molecular changes associated with silicosis and to discover potential therapeutic targets, we conducted a transcriptomics analysis of human lung tissues acquired during transplantation, which was integrated with transcriptomics and metabolomics analyses of silicosis mouse lungs. The results from the multi-omics analyses were then verified by qPCR, western blot, and immunohistochemistry. The effect of Ramatroban on the progression of silicosis was evaluated in a silica-induced mouse model. : Wide metabolic alterations were found in lungs from both human patients and mice with silicosis. Targeted metabolite quantification and validation of expression of their synthases revealed that arachidonic acid (AA) pathway metabolites, prostaglandin D (PGD) and thromboxane A (TXA), were significantly up-regulated in silicosis lungs. We further examined the effect of Ramatroban, a clinical antagonist of both PGD and TXA receptors, on treating silicosis using a mouse model. The results showed that Ramatroban significantly alleviated silica-induced pulmonary inflammation, fibrosis, and cardiopulmonary dysfunction compared with the control group. : Our results revealed the importance of AA metabolic reprogramming, especially PGD and TXA in the progression of silicosis. By blocking the receptors of these two prostanoids, Ramatroban may be a novel potential therapeutic drug to inhibit the progression of silicosis.
Topics: Animals; Biomarkers; Case-Control Studies; Female; Humans; Lung; Male; Metabolome; Mice; Prostaglandin D2; Silicosis; Thromboxane A2; Transcriptome
PubMed: 33500731
DOI: 10.7150/thno.47627 -
Ecotoxicology and Environmental Safety Oct 2022Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic...
Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic so far. Pirfenidone has consistently been shown to have anti-inflammatory and anti-fibrotic effects, but the specific mechanism by which it ameliorates fibrosis in silicosis is unclear. A rat silicosis model was established in this study, and lung tissues and serum were collected by batch execution at 14, 28, and 56 days. Also, the effects of Pirfenidone on macrophage polarization and pulmonary fibrosis were evaluated in silicosis with early intervention and late treatment by histological examination, Enzyme-linked immunosorbent assay, Hydroxyproline assay, Western blot and Quantitative reverse transcription polymerase chain reaction. The results showed that Pirfenidone significantly reduced pulmonary fibrosis in rats with silicosis, and both early intervention and late treatment effectively inhibited the expression of α-SMA, Col-I, Vimentin, Hydroxyproline, IL-1β, IL-18, and the M2 macrophage marker CD206 and Arg-1, while only early intervention effectively inhibited E-cad, TGF-β1, TNF-α, and the M1 macrophage marker iNOS, CD86. Furthermore, Pirfenidone dramatically reduced the mRNA expression of the JAK2/STAT3. These findings imply that Pirfenidone may reduce pulmonary fibrosis in silicosis rats by inhibiting macrophage polarization via the JAK2/STAT3 signaling pathway.
Topics: Animals; Fibrosis; Hydroxyproline; Interleukin-18; Janus Kinase 2; Macrophages; Pneumonia; Pulmonary Fibrosis; Pyridones; RNA, Messenger; Rats; Signal Transduction; Silicosis; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Vimentin
PubMed: 36108436
DOI: 10.1016/j.ecoenv.2022.114066 -
Surgical Pathology Clinics Jun 2024Although silicosis has been an established disease with a recognized cause for more than 100 years, many workers continue to be exposed to silica and new outbreaks of... (Review)
Review
Although silicosis has been an established disease with a recognized cause for more than 100 years, many workers continue to be exposed to silica and new outbreaks of disease continue to occur. This article describes some of the well-established and new exposures, including denim sandblasting, artificial stone cutting, and some forms of "coal worker's pneumoconiosis." The authors review the imaging and pathology of acute silicosis (silicoproteinosis), simple silicosis, and progressive massive fibrosis and summarize known and putative associations of silica exposure, including tuberculosis, lung cancer, connective tissue disease (especially systemic sclerosis), and vasculitis.
Topics: Silicosis; Humans; Occupational Exposure; Silicon Dioxide
PubMed: 38692804
DOI: 10.1016/j.path.2023.11.005 -
Nederlands Tijdschrift Voor Geneeskunde Jun 2023Silicosis is a potentially severe but preventable occupational lung disease caused by inhalation of silica particles. There is a wide application in the usage of silica...
BACKGROUND
Silicosis is a potentially severe but preventable occupational lung disease caused by inhalation of silica particles. There is a wide application in the usage of silica especially in lesser known industries. This disease has yet not been eradicated due to insufficient application of protective measures.
CASE DESCRIPTION
A 57-year-old patient presents to the pulmonary outpatient clinic with progressive dyspnea d'effort. The professional history states that he worked as a sandblaster 10 years ago. The accompanying protective measures were not properly followed by the patient at the time. The CT chest showed a nodular interstitial lung disease and silica particles were detected in the bronchial lavage conforming the diagnosis of silicosis.
CONCLUSION
Early detection of silicosis is essential to prevent further lung damage and silicosis associated complications. The occupational history and radiological diagnostics are essential to confirm the diagnosis. There is no specific treatment for silicosis. Therefore prevention is better than cure.
Topics: Male; Humans; Middle Aged; Silicosis; Lung; Silicon Dioxide; Occupational Diseases; Dyspnea; Occupational Exposure
PubMed: 37493338
DOI: No ID Found -
Journal of Hazardous Materials Jul 2023Environmental exposure to crystalline silica (CS) can lead to silicosis. Alveolar macrophages (AMs) play a crucial role in the pathogenesis of silicosis. Previously, we...
Environmental exposure to crystalline silica (CS) can lead to silicosis. Alveolar macrophages (AMs) play a crucial role in the pathogenesis of silicosis. Previously, we demonstrated that enhancing AMs mitophagy exerted protective effects on silicosis with a restrained inflammatory response. However, the exact molecular mechanisms are elusive. Pyroptosis and mitophagy are two different biological processes that determine cell fate. Exploring whether there were interactions or balances between these two processes in AMs would provide new insight into treating silicosis. Here we reported that crystalline silica induced pyroptosis in silicotic lungs and AMs with apparent mitochondria injury. Notably, we identified a reciprocal inhibitory effect between mitophagy and pyroptosis cascades in AMs. By enhancing or diminishing mitophagy, we demonstrated that PINK1-mediated mitophagy helped clear damaged mitochondria to negatively regulate CS-induced pyroptosis. While constraining pyroptosis cascades by NLRP3, Caspase1, and GSDMD inhibitors, respectively, displayed enhanced PINK1-dependent mitophagy with lessened CS-injured mitochondria. These observed effects were echoed in the mice with enhanced mitophagy. Therapeutically, we demonstrated abolishing GSDMD-dependent pyroptosis by disulfiram attenuated CS-induced silicosis. Collectively, our data demonstrated that macrophage pyroptosis interacting with mitophagy contributes to pulmonary fibrosis via modulating mitochondria homeostasis, which may provide potential therapeutic targets.
Topics: Mice; Animals; Pulmonary Fibrosis; Silicon Dioxide; Mitophagy; Pyroptosis; Macrophages; Silicosis; Protein Kinases; Mitochondria
PubMed: 37148789
DOI: 10.1016/j.jhazmat.2023.131562 -
Occupational Medicine (Oxford, England) Apr 2023
Topics: Humans; Silicosis
PubMed: 37186284
DOI: 10.1093/occmed/kqad017 -
Current Opinion in Allergy and Clinical... Apr 2021This review details recent findings related to the health effects of occupational exposure to artificial stone dust and the rapid increase in cases of artificial stone... (Review)
Review
PURPOSE OF REVIEW
This review details recent findings related to the health effects of occupational exposure to artificial stone dust and the rapid increase in cases of artificial stone associated silicosis around the world.
RECENT FINDINGS
High crystalline silica content artificial stone is now commonly used for the production of kitchen benchtops. Reports of artificial stone silicosis from many countries have noted that workers were typically employed at small workplaces and were often diagnosed in their 30s or 40s. Poor exposure control measures were common, including the practice of 'dry processing'. Dust generated from artificial stone has been noted to have properties that influence toxicity, including high silica content, generation of nanosized particles and presence of metals and resins. Artificial stone silicosis differs from silicosis associated with other occupational settings including shorter latency and rapid disease progression. High-resolution computed tomography (CT) chest imaging of artificial stone silicosis has often noted the presence of ground glass opacities, which may not be detected in chest x-ray screening. Increased prevalence of autoimmune disease, such as scleroderma, has also been reported in this industry.
SUMMARY
Further evaluation of the safety of work with artificial stone is required, including the effectiveness of dust control measures. Current reports of artificial stone silicosis indicate the potential for widespread undiagnosed respiratory disease in this industry. Provision of more sensitive health screening methods for all at-risk workers and the development of new treatment options particularly for this form of silicosis is urgently required.
Topics: Dust; Humans; Occupational Exposure; Silicon Dioxide; Silicosis; Workplace
PubMed: 33332924
DOI: 10.1097/ACI.0000000000000715 -
American Journal of Industrial Medicine Aug 2023Silicosis is a fibrotic lung disease caused by exposure to respirable crystalline silica. Historically, silicosis was common among miners and other professions in the...
BACKGROUND
Silicosis is a fibrotic lung disease caused by exposure to respirable crystalline silica. Historically, silicosis was common among miners and other professions in the 20th century, and in recent decades has re-emerged in coal mining and appeared in new workplaces, including the manufacture of distressed jeans and artificial stone countertops.
METHODS
Physician billing data for the province of Ontario between 1992 and 2019 were analyzed across six time-periods (1993-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015, and 2016-2019). The case definition was two or more billing records within 24 months with a silicosis diagnosis code (ICD-9 502, ICD-10 J62). Cases from 1993 to 1995 were excluded as prevalent cases. Crude incidence rates per 100,000 persons were calculated by time-period, age, sex, and region. Analyses were repeated in parallel for pulmonary fibrosis (PF) (ICD-9 515, ICD-10 J84) and asbestosis (ICD-9 501; ICD-10 J61).
RESULTS
From 1996 to 2019, 444 cases of silicosis, 2719 cases of asbestosis and 59,228 cases of PF were identified. Silicosis rates decreased from 0.42 cases per 100,000 in 1996-2000 to 0.06 per 100,000 people in 2016-2019. A similar trend was observed for asbestosis (1.66 to 0.51 per 100,000 persons) but the incidence rate of PF increased from 11.6 to 33.9 per 100,000 persons. Incidence rates for all outcomes were higher among men and older adults.
CONCLUSIONS
A decreasing incidence of silicosis was observed in this analysis. However, the incidence of PF increased, consistent with findings from other jurisdictions. While cases of silicosis have been recorded among artificial stone workers in Ontario these cases do not seem to have impacted the population rates thus far. Ongoing, periodic surveillance of occupational diseases is helpful for tracking population-level trends over time.
Topics: Male; Humans; Aged; Asbestosis; Pulmonary Fibrosis; Ontario; Silicosis; Silicon Dioxide; Occupational Exposure
PubMed: 37302125
DOI: 10.1002/ajim.23504 -
Revue Des Maladies Respiratoires Mar 2021Pneumoconiosis is defined as a diffuse interstitial lung disease secondary to inhalation of mineral particles. Haemoptysis is common in pneumoconiosis. But it is usually...
INTRODUCTION
Pneumoconiosis is defined as a diffuse interstitial lung disease secondary to inhalation of mineral particles. Haemoptysis is common in pneumoconiosis. But it is usually secondary to bronchiectasis, bronchitis or pulmonary tuberculosis occurring with silicosis.
OBSERVATION
A 74-year-old Portuguese man, known to have chronic respiratory failure secondary to chronic silicosis, was treated for moderate haemoptysis. CT angiography revealed bilateral fibrosing peri-hilar masses, inferior lobe nodules and previously known mediastinal lymphadenopathy, without active bleeding. Fibreoptic bronchoscopy showed an anthracotic appearance with lesions typical of silicosis on pathological examination of trans-bronchial biopsies and needle aspiration of mediastinal adenopathy by endobronchial ultrasound.
CONCLUSION
After a full aetiological assessment, no cause other than silicosis has been identified. Haemoptysis is frequently observed in silicosis, but it results from silicosis complications. It is not a classic complication of isolated silicosis.
Topics: Aged; Bronchoscopy; Hemoptysis; Humans; Lung Diseases, Interstitial; Male; Mediastinal Diseases; Silicosis
PubMed: 33612346
DOI: 10.1016/j.rmr.2021.01.012